scholarly journals Genomic Alteration in Metastatic Breast Cancer and Its Treatment

2020 ◽  
pp. 30-43
Author(s):  
Allen Li ◽  
Stephen M. Schleicher ◽  
Fabrice Andre ◽  
Zahi I. Mitri
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Mutation Detection ◽  
Pik3ca Mutation ◽  
Metastatic Breast ◽  
Detection Methods ◽  
Genomic Alteration ◽  
Therapeutic Approaches ◽  
Genomic Alterations

Metastatic breast cancer (mBC) remains responsible for the majority of breast cancer deaths. Whereas clinical outcomes have improved with the development of novel therapies, resistance almost inevitably develops, indicating the need for novel therapeutic approaches for the treatment of mBC. Recent investigations into mBC genomic alterations have revealed novel and potential therapeutic targets. Most notably, therapies against PIK3CA mutation and germline BRCA1/2 mutations have solidified the role of targeted therapy in mBC, with treatments against these alterations now approved by the U.S. Food and Drug Administration (FDA) on the basis of clinical benefit for patients with mBC. Familiarity with relevant genomic alterations in mBC, technologies for mutation detection, methods of interpreting genomic alterations, and an understanding of their clinical impact will aid practicing clinicians in the treatment of mBC as the field of breast oncology moves toward the era of precision medicine.

Cancer gene profile of metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1015-1015 ◽  
Author(s):  
Funda Meric-Bernstam ◽  
Garrett Frampton ◽  
Jaime Ferrer-Lozano ◽  
Roman Yelensky ◽  
Gary A. Palmer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Point Mutations ◽  
Metastatic Breast ◽  
Genomic Alteration ◽  
Genomic Profiling ◽  
Genomic Alterations ◽  
Primary Tumors ◽  
Recurrent Tumors

1015 Background: There is great interest in using genomic information to guide therapy selection in cancer patients. The aim of this study was to determine the spectrum of genomic alterations identified in MBC patients, and evaluate the concordance of alterations between primary and recurrent tumors. Methods: We performed comprehensive profiling on formalin-fixed paraffin embedded samples from 42 patients with MBC using a targeted next generation sequencing (NGS) assay in a CLIA laboratory (Foundation Medicine). Genomic libraries were captured for 3,230 exons in 182 cancer related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to an average depth of 390X with 99% of bases covered >100X. In total 30 primary and 37 recurrent tumors were profiled, including 3 separate recurrences in 1 patient and matched primary-recurrences in 22 patients. Point mutations, indels, copy number alterations and rearrangements were assessed. Alterations that are targetable with established or investigational therapeutics were considered “actionable”. Results: At least 1 genomic alteration was identified in all but 2 breast samples (both primary tumors). Point mutations were identified in several cancer-related genes including PIK3CA, TP53, PTEN, CDH1, ARID1A, AKT1, NF1, FBXW7 and FGFR3. Amplification was observed in HER2; 11 of 12 HER2 IHC positive samples were found to have HER2 gains by NGS; in addition, a HER2 gain was identified by NGS in a HER2- (1+ IHC) sample. Amplification of PIK3CA, IGF1R, FGFR2, AKT2, MDM2, and MCL1 plus a CDKN2A homozygous deletion were also identified. While the majority of known driver alterations (85%) were concordant in the matched pairs of primary and recurrent tumors, in 11 of 22 sets there was at least 1 discordant driver alteration, and these included both gains and losses of potential therapeutic targets. Overall 32 of 42 patients (76%) had an actionable genomic alteration. Conclusions: Genomic profiling of breast cancer samples reveals genomic alterations in most metastatic breast cancer patients. Over three quarters of patients have actionable findings, suggesting that genomic profiling may assist in individualized pathway-directed therapy.

Next-generation sequencing (NGS) for personalized therapy in metastatic breast cancer: Selection of therapy and outcomes.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23166-e23166
Author(s):  
Jessica Ribeiro Gomes ◽  
Raphael Brandao Moreira ◽  
Matheus Bongers Alessandretti ◽  
Marcelo Rocha De Sousa Cruz
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Next Generation Sequencing ◽  
Clinical Benefit ◽  
Metastatic Breast ◽  
Personalized Therapy ◽  
Genomic Alterations ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

e23166 Background: Treatment for metastatic breast cancer (MBC) has been driven by hormone receptors, HER2 expressions or their absence. Resistance to therapy and progressive disease will occur and empirical chemotherapy lines usually are the next steps. We aim to analyze the role of next-generation sequencing (NGS) for a personalized therapy in metastatic breast cancer and its potential clinical benefit. Methods: We included patients diagnosed with MBC treated at Centro Oncologico Antonio Ermirio de Moraes – Brazil from April 2013 to December 2016. All patients had metastasis accessible for biopsy. The tumor tissue was stored in paraffin and then analyzed by NGS-based assay that identifies genomic alterations within 236 genes. Results: 19 patients with MBC were evaluated (10 triple-negative; 4 HER2-positive; 5 hormonal receptor positive/HER2-negative). The most frequent and relevant genomic alterations identified by NGS assay were in the following genes: 13 TP53 (68.4%); 4 ERBB2 (21%); 4 PTEN (21%); 4 FGFR (21%); 3 PIK3CA (15.8%); 2 BRCA (10.5%); 2 ATM (10.5%); 2 AKT (10.5%); 2 MYC (10.5%); 1 CCND1 (5.3%); and 1 KRAS (5.3%). The NGS assay was able to suggest further therapy in 16/19 patients (84%). The suggested therapies would not be an empirical option according to the cancer’s subtype in 12/16 patients (75%). Therapy could be personalized in nine patients, across multiple lines of therapies (median of 5th line, with a range of 1-14). Median PFS was 6 months, and 8/9 patients (90%) achieved an objective response with the treatment indicated by NGS. Therefore, the assay provided clinical benefit in 42% of patients. Conclusions: NGS panel identified potentially actionable alterations in the majority of patients with MBC (84%). The overall clinical benefit with use of NGS-based assay was 42%. Further studies are necessary to better evaluate the role of NGS for a personalized therapy in MBC.

scholarly journals Association of a novel circulating tumor DNA next-generating sequencing platform with circulating tumor cells (CTCs) and CTC clusters in metastatic breast cancer

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew A. Davis ◽  
Qiang Zhang ◽  
Lorenzo Gerratana ◽  
Ami N. Shah ◽  
Youbin Zhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Genomic Alteration ◽  
Genomic Alterations ◽  
Disease Heterogeneity ◽  
Tumor Dna

Abstract Purpose Liquid biopsies, including circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), can be used to understand disease prognosis, tumor heterogeneity, and dynamic response to treatment in metastatic breast cancer (MBC). We explored a novel, 180-gene ctDNA panel and the association of this platform with CTCs and CTC clusters. Methods A total of 40 samples from 22 patients with MBC were included in the study. For the primary analysis, all patients had ctDNA sequencing using the PredicinePLUS™ platform. CTCs and CTC clusters were examined using the CellSearch™ System. Clinical and pathological variables were reported using descriptive analyses. Associations between CTC count and specific genomic alterations were tested using the Mann-Whitney U test. Results Of 43 sequenced patients, 40 (93%) had at least one detectable genomic alteration with a median of 6 (range 1–22). Fifty-seven different genes were altered, and the landscape of genomic alterations was representative of MBC, including the commonly encountered alterations TP53, PTEN, PIK3CA, ATM, BRCA1, CCND1, ESR1, and MYC. In patients with predominantly hormone-receptor-positive MBC, the number of CTCs was significantly associated with alterations in ESR1 (P < 0.005), GATA3 (P < 0.05), CDH1 (P < 0.0005), and CCND1 (P < 0.05) (Mann-Whitney U test). Thirty-six percent of patients had CTC clusters, which were associated with alterations in CDH1, CCND1, and BRCA1 (all P < 0.05, Mann-Whitney U test). In an independent validation cohort, CTC enumeration confirmed significant associations with ESR1 and GATA3, while CTC clusters were significantly associated with CDH1. Conclusions We report on a novel ctDNA platform that detected genomic alterations in the vast majority of tested patients, further indicating potential clinical utility for capturing disease heterogeneity and for disease monitoring. Detection of CTCs and CTC clusters was associated with particular genomic profiles.

Role of rebiopsy in metastatic breast cancer at progression

2019 ◽  
Vol 43 (5) ◽  
pp. 438-442 ◽  
Author(s):  
Manish Sharma ◽  
Ajay Gogia ◽  
Suryanarayana S.V. Deo ◽  
Sandeep Mathur
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast
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